5aad

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'''Unreleased structure'''
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==Aurora A kinase bound to an imidazopyridine inhibitor (7a)==
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<StructureSection load='5aad' size='340' side='right' caption='[[5aad]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5aad]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AAD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AAD FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5GX:7-(1-BENZYL-1H-PYRAZOL-4-YL)-6-CHLORO-2-(1,3-DIMETHYL-1H-PYRAZOL-4-YL)-3H-IMIDAZO[4,5-B]PYRIDINE'>5GX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5aae|5aae]], [[5aaf|5aaf]], [[5aag|5aag]]</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5aad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aad OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5aad RCSB], [http://www.ebi.ac.uk/pdbsum/5aad PDBsum]</span></td></tr>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN]] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Introduction of a 1-benzyl-1H-pyrazol-4-yl moiety at C7 of the imidazo[4,5-b]pyridine scaffold provided 7a which inhibited a range of kinases including Aurora-A. Modification of the benzyl group in 7a, and subsequent co-crystallisation of the resulting analogues with Aurora-A indicated distinct differences in binding mode dependent upon the pyrazole N-substituent. Compounds 7a and 14d interact with the P-loop whereas 14a and 14b engage with Thr217 in the post-hinge region. These crystallographic insights provide options for the design of compounds interacting with the DFG motif or with Thr217.
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The entry 5aad is ON HOLD until Jul 24 2017
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7-(Pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine-based derivatives for kinase inhibition: Co-crystallisation studies with Aurora-A reveal distinct differences in the orientation of the pyrazole N1-substituent.,Bavetsias V, Perez-Fuertes Y, McIntyre PJ, Atrash B, Kosmopoulou M, O'Fee L, Burke R, Sun C, Faisal A, Bush K, Avery S, Henley A, Raynaud FI, Linardopoulos S, Bayliss R, Blagg J Bioorg Med Chem Lett. 2015 Aug 6. pii: S0960-894X(15)00827-6. doi:, 10.1016/j.bmcl.2015.08.003. PMID:26296477<ref>PMID:26296477</ref>
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Authors: McIntyre, P.J., Kosmopoulou, M., Bayliss, R.
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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Description: Aurora A kinase bound to an imidazopyridine inhibitor (7a)
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== References ==
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[[Category: Unreleased Structures]]
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<references/>
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[[Category: Mcintyre, P.J]]
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__TOC__
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</StructureSection>
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Bayliss, R]]
[[Category: Kosmopoulou, M]]
[[Category: Kosmopoulou, M]]
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[[Category: Bayliss, R]]
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[[Category: McIntyre, P J]]
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[[Category: Aurora kinase]]
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[[Category: Aurora-a]]
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[[Category: Imidazopyridine]]
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[[Category: Inhibitor]]
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[[Category: Transferase]]

Revision as of 12:19, 2 September 2015

Aurora A kinase bound to an imidazopyridine inhibitor (7a)

5aad, resolution 3.10Å

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